CD4+ T cell inducible immunoregulatory cytokine response in rheumatoid arthritis.

OBJECTIVE

Monocytes and CD4+/CD8+ T cells produce immunoregulatory cytokines that participate in the pathogenesis of various immune disorders. We investigated the secretion of Th1-Th2 cell response cytokine production of CD4+/CD8+ T cells from the synovial fluid (SF) and blood of patients with rheumatoid arthritis (RA).

METHODS

Blood and SF purified monocytes, CD4+ and CD8+ T cells were stimulated with bacterial lipopolysaccharides or anti-CD3 antibody, and secretion of various cytokines was determined by bioassay or ELISA:

RESULTS

Monocytes from SF and blood of patients with RA produced highly elevated levels of interleukin-1 alpha (IL-1 alpha), IL-6, tumor necrosis factor-alpha (TNF-alpha), and granulocyte macrophage colony stimulating factor (GMCSF), the leading mediators of inflammation. However, CD4+ T cells secreted deficient levels of IL-2 and interferon-gamma (IFN-gamma), but higher levels of IL-4 and IL-10, the typical immunoregulatory Th2 cell response cytokines. CD8+ T cells also produce elevated levels of IL-4 and IL-10 but almost normal levels of IFN-gamma in this disease.

CONCLUSION

The cytokine produced by monocytes (IL-alpha, IL-6, TNF-alpha, and GMCSF) and by CD4+ T cells Th2 cell responses (IL-4 and IL-10) may exert immunopathologic and immunoregulatory effects in SF and thus mediate some of the clinical manifestations of RA.